Over the past year, there has been great excitement among callers to the IMF Hotline and postings on the internet list serve about the new drug VELCADE™ (Millennium Pharmaceuticals). It was decided that it would be of great interest to interview participants in the recent phase II trials to give readers a better direct knowledge of the impact of VELCADE™ therapy in patients with relapsing/refractory myeloma.

Compiled by Dr. Brian G.M. Durie from patient interviews

Alta Bates Cancer Center in Berkeley, California, and the team of doctors, nurses, and coordinators in the clinical trials group were major contributors to the phase II experience with PS-341 (now known as VELCADE™) in multiple myeloma. Patients relapsing and refractory to prior therapy were entered into the Millennium-sponsored phase II multi-center study, which accrued 201 patients.

Because of early evidence of benefit in the phase I study conducted at the University of North Carolina at Chapel Hill, there was tremendous interest and excitement among patients. The stories of 3 patients highlight the impact for patients typically in desperate need of a new treatment that will work well without too much toxicity.

SP, a retired 50 year-old African-American lady, was one such patient. Diagnosed in 1998, she had previously had a stem cell transplant with remission that lasted for about a year. When the myeloma grew back so soon, she was keen to try something new and different. So 6 months ago, treatment started with the PS-341 being administered intravenously over 3-5 seconds, twice/week for 2 weeks, followed by a 10 day rest period in each cycle. In her case, dexamethasone was added eventually to the PS-341 treatment. After 2-3 months she was responding well and has achieved an excellent remission. Her bone pain was much improved, anemia better, and myeloma protein level substantially reduced. A follow up bone marrow test showed complete remission. She is clearly a believer that PS-341 works. In her case, she had not taken thalidomide in the past, so she did not have neuropathy to contend with. There has been only slight tingling in her toes. Her main complaint was she got extremely bored, sitting around all the time, waiting for follow-up testing, and the like. She strongly recommends that anyone considering new treatment look into possible PS-341 protocols in their area.

RA is a 72 year-old retired real estate agent first diagnosed in June 1999. His initial therapy was melphalan/prednisone plus radiation treatment to an area of bone disease. Because of his age, it was felt that he was not an ideal candidate for stem cell transplant. So when he was not responding well, alternate therapy was sought. Starting in 2001, it has now been over a year since the first dose of PS-341. He tolerated it well and like SB has had an excellent response. Follow-up bone marrow showed dramatic improvement. No added dexamethasone was needed in his case. He did develop some neuropathy in his feet and takes neurontin for that. The problem with his feet consisted of what felt like “electric shocks” plus some numbness in between. He received a total of 5 cycles of PS-341 and has been followed on pamidronate (Aredia®) treatment alone since then. The treatment course was complicated by an episode of pneumonia, as well as a strange, unexplained episode when he unexpectedly fell out of a chair. But now he is active and doing very well. His very good response also makes him a strong advocate for VELCADE™ for any other patients in need of new treatment. He is particularly pleased that he continues to be in remission, without any additional therapy.

CB is a 69 year-old retired computer operator diagnosed in 1995. She had multiple therapies over the years, including VAD and other types of chemotherapy. She had also been on the Dendreon vaccine clinical trial, which was not helpful in her case. Unfortunately, her treatment is complicated by her diabetes. Prior to the PS-341 she was taking thalidomide (Thalomid™) 400mg a day and “felt like a zombie.” In May 2001, she enrolled in a trial with PS-341 on the recommendation of Dr. Jeffrey Wolf. She was very excited to have a chance to “get into the new trial.” When research coordinator Beth Davis told her that the next patient number in the protocol was 13, she knew it would be lucky 13 for her! After one month she was already responding very well. No additional dexamethasone was needed. Her main problem was the worsening of the neuropathy, which she had because of the prior thalidomide. The bone pain, anemia, and myeloma protein levels all improved. After 6 cycles of treatment, bone marrow testing showed complete remission. Since then, she has continued on Aredia maintenance. Currently, she is back to normal mentally, but physically she is upset because she just can’t get rid of the neuropathy caused by the thalidomide. The important fact is that her remission continues, and that makes her happy.

These three patient experiences highlight participation in Millennium sponsored PS-341 phase II clinical trials. It is important to note that not all patients responded. Preliminary analysis indicated that around 10% of patients in the first cohort were complete responders with another 30-40% of patients achieved good partial responses. Other patients have noted additional side effects including some fatigue, especially with an increased number of cycles of PS-341. Mild diarrhea and some reduction in blood counts including anemia and reduced platelet count levels have occurred. The opportunity to have access to PS-341 was welcomed by patients all needing “something to really work” to “get the myeloma into remission.” There is no doubt that already PS-134 has been a success for the responding patients. How long will their remissions last? We don’t know. However, we know that several patients in the meantime have relapsed and needed alternate therapy. Only time will tell what the average length of remission will be. Looking to the future there is great excitement that up front use of PS-341 can provide a greater benefit. Patients who have not had thalidomide can hopefully avoid the neuropathy. Combinations with other drugs, including the thalidomide analog Revimid™, which is not neurotoxic and/or melphalan, can potentially give added benefit. At this point, the outlook is promising in a disease, for which until recently there were so few drugs that could really make a difference.